Abstract
There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Although repurposed drugs with favorable safety profiles could have significant benefit, widely available prevention or treatment options for COVID-19 have yet to be identified. Efforts to identify approved drugs with in vitro activity against SARS-CoV-2 resulted in identification of antiviral sigma-1 receptor ligands, including antihistamines in the histamine-1 receptor binding class. We identified antihistamine candidates for repurposing by mining electronic health records of usage in population of more than 219,000 subjects tested for SARS-CoV-2. Usage of diphenhydramine, hydroxyzine and azelastine was associated with reduced incidence of SARS-CoV-2 positivity in subjects greater than age 61. We found diphenhydramine, hydroxyzine and azelastine to exhibit direct antiviral activity against SARS-CoV-2 in vitro. Although mechanisms by which specific antihistamines exert antiviral effects is not clear, hydroxyzine, and possibly azelastine, bind Angiotensin Converting Enzyme-2 (ACE2) and the sigma-1 receptor as off-targets. Clinical studies are needed to measure the effectiveness of diphenhydramine, hydroxyzine and azelastine for disease prevention, for early intervention, or as adjuvant therapy for severe COVID-19.
Keywords: Angiotensin converting Enzyme-2; Docking; Repurposing; SARS-CoV-2; Sigma-1 receptor.
【저자키워드】 SARS-CoV-2, repurposing, docking, Angiotensin converting enzyme-2, sigma-1 receptor, 【초록키워드】 COVID-19, Treatment, ACE2, therapy, Repurposed drugs, severe COVID-19, Antiviral, SARS-COV-2 infection, Intervention, antiviral effects, docking, in vitro, antiviral activity, outcome, angiotensin converting enzyme, Electronic health record, approved drugs, Antiviral effect, Angiotensin converting enzyme-2, Repurposed drug, clinical, Effectiveness, Clinical studies, age, receptor, incidence, disease, mechanism, safety profile, COVID-19 patients, Antihistamine, in vitro activity, angiotensin, Histamine, Receptor binding, Electronic health records, adjuvant therapy, azelastine, hydroxyzine, diphenhydramine, approved drug, Antihistamines, Usage, subject, enzyme, ligands, SARS-CoV-2 positivity, candidate, sigma, Prevent, benefit, IMPROVE, greater, tested, identify, reduced, 【제목키워드】 COVID-19, Antiviral, identification,